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Project description:Clinical infection caused by carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) is gradually increasing and spreading across the world, and phage therapy is a viable application as an alternative to antibiotics. However, additional clinical application is still restricted by the phage resistance. In order to further explore the mechanism of phage resistance, particularly the difference between in vivo and in vitro. Here, we used a mouse intra-abdominal infection (IAI) model to evaluate the antibacterial properties of two lytic phages and further isolated and characterized phage-resistant mutants. Finally, we determined through genomic and transcriptomic analysis that most of the mutation sites in the resistant mutants were located in the capsular polysaccharides gene cluster. However, RM01 and RM12 developed phage resistance by downregulating capsular polysaccharide (CPS) and its transcriptional regulators without any mutations in the CPS gene. In summary, these findings provided further evidence in phage therapy, particularly in addressing the issue of CR-hvKP infections.
2025-09-18 | MTBLS12480 | MetaboLights
Project description:Intestinal colonization by Klebsiella pneumoniae is recognized as a pivotal prerequisite for its systemic dissemination and subsequent invasive infection; however, the metabolic basis and regulatory mechanisms underlying this process remain poorly understood. In this study, we employed transposon insertion sequencing (Tn-seq) to systematically identify metabolic genes associated with intestinal colonization in hypervirulent Klebsiella pneumoniae (hvKp). By integrating high-throughput screening with in vivo phenotypic validation, we identified the global transcriptional regulator DksA as a key factor that markedly enhances hvKp intestinal colonization. Mechanistically, DksA appears to promote colonization by enhancing carbon source metabolism. Combined transcriptomic analyses with homology modeling and molecular dynamics simulations further revealed that DksA induces cascade allosteric remodeling of key RNA polymerase structural domains, thereby enhancing hvKp utilization of common intestinal carbon sources and facilitating intestinal colonization. Collectively, our findings highlight the critical role of transcriptionally regulated metabolic plasticity in hvKp intestinal colonization and provide a theoretical framework and potential targets for developing anti-colonization strategies that exploit pathogen metabolic vulnerabilities.
2026-03-18 | GSE324122 | GEO
Project description:High-resolution single-cell RNA-seq reveals the immune landscape of hvKp-infected lungs
2023-12-26 | GSE220594 | GEO